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J Neurol Sci. 2015 May 15;352(1-2):29-33. doi: 10.1016/j.jns.2015.02.007. Epub 2015 Apr 2.

Exome sequencing identifies a novel intronic mutation in ENG that causes recurrence of pulmonary arteriovenous malformations.

Author information

1
Department of Stroke Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan. Electronic address: sajink@me.com.
2
Department of Clinical Neuroscience, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan. Electronic address: tkawarai@tokushima-u.ac.jp.
3
Department of Clinical Neuroscience, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan. Electronic address: ninigii@gmail.com.
4
Department of Stroke Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan. Electronic address: sato.takabee1987@gmail.com.
5
Department of Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.. Electronic address: morino@hiroshima-u.ac.jp.
6
Laboratorio di Neurogenetica, CERC-IRCCS Santa Lucia, Rome, Italy; Dipartimento di Medicina dei Sistemi, Università di Roma "Tor Vergata", Rome, Italy. Electronic address: a.orlacchio@hsantalucia.it.
7
Department of Clinical Neuroscience, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan. Electronic address: okkey19840323@gmail.com.
8
Department of Stroke Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan. Electronic address: k-kimura@nms.ac.jp.
9
Department of Clinical Neuroscience, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan. Electronic address: rkaji@tokushima-u.ac.jp.

Abstract

Hereditary hemorrhagic telangiectasia (HHT) occasionally can be discovered in patients with cerebrovascular disease. Pulmonary arteriovenous malformation (PAVM) is one of the complications in HHT and occasionally is causative for life-threatening embolic stroke. Several genetic defects have been reported in patients with HHT. The broad spectrum of phenotype and intrafamilial phenotype variations, including age-at-onset of vascular events, often make an early diagnosis difficult. We present here a Japanese family with a novel intronic heterozygous mutation of ENG, which was identified using whole exome sequencing (WES). The intronic mutation, IVS3+4delAGTG, results in in-frame deletion of exon 3 and would produce a shorter ENG protein lacking the extracellular forty-seven amino acid sequences, which is located within the orphan domain. Our findings highlight the importance of the domain for the downstream signaling pathway of transforming growth factor-beta and bone morphogenesis protein superfamily receptors. Considering the phenotype variations and the available treatment for vascular complications, an early diagnosis using genetic testing, including WES, should be considered for individuals at risk of HHT.

KEYWORDS:

Aberrant transcript; Arteriovenous malformation; Endoglin; Hereditary hemorrhagic telangiectasia; Intronic mutation; Whole exome sequencing

PMID:
25868896
DOI:
10.1016/j.jns.2015.02.007
[Indexed for MEDLINE]

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